Hong Kong Journal of Nephrology

Volume 5 Number 2, 2003
Abstract

A Study of Tubular Dysfunction in Indian Patients With Lupus Nephritis

Krishan Lal Gupta, Thangamani Muthukumar, Anand Dotial, Rajendra Prasad, Kusum Joshi, Vivekanand Jha, Harbir Singh Kohli, Kamal Sud, Nirmal Kumar Ganguly, Vinay Sakhuja

Background: Most reports mention isolated tubular dysfunction in active lupus nephritis and, hence, the present study was designed to investigate varied functional defects in Indian patients with stable lupus nephritis.

Methods: Twenty patients with lupus nephritis were evaluated for evidence of renal tubular functional abnormalities. Disease activity was studied using the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Renal histology was available for 12 patients, including six with WHO class IV disease and three each with class III and class V disease. Analysis of activity and chronicity indices as well as severity of tubulointerstitial involvement was also done on these biopsy specimens. Estimation of fractional excretion (FE) of beta-2 microglobulin (β2μg), 24-hour urinary excretion of alkaline phosphatase (ALP), leucine aminopeptidase (LAP) and gamma-glutamyltransferase (GGT), as well as the short ammonium chloride (NH4Cl) test, were performed in all patients. Ten healthy volunteers served as controls.

Results: The mean creatinine clearance (Ccr) was 58.9 ± 19.1 mL/min (range, 24.5-104.3 mL/min). Serum β2μg and FE-β2μg were elevated in all patients (mean, 5.5 ± 1.4 mg/L and 1.6 ± 0.9%, respectively). Urinary ALP excretion was elevated in 65% of patients, with a mean of 6.88 ± 5.08 μmol/L/min, and urinary GGT excretion was elevated in 50% of patients, with a mean of 59.43 ± 33.70 μmol/L/min. There was no significant correlation of serum β2μg, FE-β2μg, and urinary ALP levels with Ccr or severity of proteinuria. Urinary GGT levels were increased proportionately to the decrease in Ccr. Only 20% of patients were unable to acidify their urine (pH < 5.3); the minimum urinary pH was higher in the lupus nephritis patients compared to controls (5.17 ± 0.58 vs 4.65 ± 0.26; p < 0.05). The mean baseline and peak titratable acidity were not significantly lower in lupus nephritis patients. There was significant correlation of all renal functional abnormalities with the severity of SLEDAI and tubulo-interstitial involvement.

Conclusions: Both proximal and distal tubular functional abnormalities were seen in patients with lupus nephritis and can co-exist. FE-β2μg is the most sensitive indicator of proximal tubal dysfunction. Assessment of urinary enzymes may give an early indication of tubular dysfunction. Disease activity and severity of tubulo-interstitial involvement influence these abnormalities. [Hong Kong J Nephrol 2003;5(2):90-7]

Key words: acidification defects, beta-2 microglobulin, lupus nephritis, tubular dysfunction, urinary enzyme excretion

背景: 至今,大部分有關腎小管功能障礙的研究,均以活性狼瘡性腎炎患者的單一腎小管功能障礙為主題﹔本研究則以穩定型狼瘡性腎炎(印度裔)患者為對象 (n = 20),對多項腎功能障礙作出調查。

方法: 病人的病況依系統性紅斑性狼瘡疾病活動指數 (SLEDAI) 分類,其中有12人的腎臟組織切片可供腎小管-間質病變的分析,包括WHO狼瘡性腎炎分級第IV級共6人、及第III級與第V級各3人。對於所有病人,腎小管功能的測量項目包括beta-2 microglobulin排泄比例(FE- 2μg)、alkaline phosphatase (ALP)、leucine aminopeptidase (LAP)、與gamma-glutamyltransferase (GGT) 之24小時尿排泄量、及簡短 ammonium chloride (NH4Cl) 測試 。對照組則為10位健康自願者。

結果: 病人之平均creatinine廓清率 (Ccr) 為58.9 mL/min (範圍24.5-104.3 mL/min)。在所有病人中,血清 2μg 及 FE- 2μg 均偏高 (平均分別為5.5 ± 1.4 mg/L及1.6 ± 0.9%)。ALP及GGT尿排泄量的升高則分別出現於65% (平均6.88 ± 5.08 μmol/L/min) 及50% (平均59.43 ± 33.70 μmol/L/min) 的病人。不論是血清 2μg、FE- 2μg、或尿中ALP濃度,均與Ccr或蛋白尿嚴重性之間缺乏關聯性。尿中GGT濃度則與Ccr呈反比。病人中只有20%未能有效達到尿液的酸化 (pH < 5.3)。與對照組相比,狼瘡性腎炎患者的最低尿液 pH 值明顯較高 (5.2 ± 0.6 vs 4.7 ± 0.3; p < 0.05)﹔但其平均基線酸度及最高可滴定酸度並非明顯較低。分析顯示,所有腎功能異常與SLEDAI及腎小管-間質病變嚴重性之間,均存在顯著的關聯性。

結論: 近端及遠端小管的功能異常均可見於狼瘡性腎炎患者中,兩者亦可共同存在。FE- 2μg 是近端小管功能障礙的最敏感指標,而尿液酵素的評估則有助於小管功能障礙的早期偵測。這些腎功能異常均受SLE疾病活動及腎小管-間質病變的影響。


Back to Previous Page